Adjunctive sepsis therapy with aminophylline (STAP): a randomized controlled trial

Abstract BackgroundSepsis is a serious disease that is often caused by infection. Aminophylline has anti-asthma and anti-inflammatory effects. We aimed to explore the safety and effect of aminophylline in sepsis.MethodsWe conducted a clinical randomized controlled trial involving 100 patients diagnosed with sepsis within 48 hours after ICU (intensive care unit) admission in two sites (First Affiliated Hospital of Zhengzhou University and First Affiliated Hospital of Kunming Medical University). All patients were randomized in a 1:1 ratio to receive standard therapy with or without aminophylline. The primary clinical outcome was all-cause mortality at 28 days.ResultsFrom 27 September 2018 to 12 February 2020, we screened 277 septic patients and eventually enrolled 100 patients, with 50 assigned to the aminophylline group and 50 to the usual-care group. At 28 days, 7 of 50 patients (14.0%) in the aminophylline group had died, compared with 16 of 50 (32.0%) in the usual-care group (P = 0.032). Cox regression showed that the aminophylline group had a lower risk of death (HR = 0.312, 95%CI: 0.129–0.753). Compared with the usual-care group, patients in the aminophylline group had a longer survival time (P = 0.039 by the log-rank test). With the extension of the treatment time, the effect of aminophylline on the doses of vasopressors, oxygenation index, and SOFA score increased. There were no significant differences in total hospitalization days, ICU hospitalization days, and rates of serious adverse events (all P > 0.05). No adverse events were observed in the trial.ConclusionsAminophylline as an adjunct therapy could significantly reduce the risk of death and prolong the survival time of patients with sepsis.Trial registrationThe trial was registered at the Chinese clinical trial registry (ChiCTR1800019173), 29 October 2018 - retrospectively registered, http://www.chictr.org.cn/index.aspx